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Mapping the human genetic architecture of COVID-19

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Title: Mapping the human genetic architecture of COVID-19
Authors: COVID-19 Host Genetics Initiative
Item Type: Journal Article
Abstract: The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3-7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
Issue Date: 8-Jul-2021
Date of Acceptance: 23-Jun-2021
URI: http://hdl.handle.net/10044/1/92821
DOI: 10.1038/s41586-021-03767-x
ISSN: 0028-0836
Publisher: Nature Research
Start Page: 472
End Page: 477
Journal / Book Title: Nature
Volume: 600
Copyright Statement: © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Sponsor/Funder: UK Research and Innovation
UK Research and Innovation
UKRI MRC COVID-19 Rapid Response Call
Funder's Grant Number: 1257927
9815274 MC_PC_19025
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
COVID-19 Host Genetics Initiative
General Science & Technology
Publication Status: Published
Conference Place: England
Open Access location: https://www.nature.com/articles/s41586-021-03767-x
Online Publication Date: 2021-07-08
Appears in Collections:Department of Metabolism, Digestion and Reproduction
Department of Surgery and Cancer
Department of Infectious Diseases
National Heart and Lung Institute
Faculty of Medicine
Imperial College London COVID-19

This item is licensed under a Creative Commons License Creative Commons